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HMB200H1 (140)
Lecture

HMB200 2014 Lecture 21.pdf

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Department
Human Biology
Course Code
HMB200H1
Professor
John Yeomans

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  Lecture  21:  Brain  Growth  and  Neural  Connections     Postnatal  Brain  Growth   -­‐ at  birth,  don’t  want  too  big  of  a  brain  weight  because  a  big   head  is  hard  to  get  out  from  birth  canal   -­‐ after  birth,  neurons  become  larger;  brain  weight  goes  up,   volume  of  each  neurons  gets  bigger   –  growing  more   dendrites  to  contact,  growing  lots  of  myelin  (last  process  that   continues  after  birth),  growing  many  more  s ynapses/neuron   -­‐ maturing  of  neurons,  then  connections,  then  myelin  after   birth   -­‐ the  number  of  neurons  is  usually  established  already   -­‐ neurons  have  chemicals  that  can  differentiate  their  differentiation     Neurotropic  Factors   • Proteins  expressed  in  specific  neurons   • Cell  survival  is  stimulated  by  neurotropic  factors   • Improve  survival  of  cells  and  synaptic  connections,  neurite  growth,  and  plasticity  (changes  in  synaptic  strength).   • Nerve  Growth  Factor:  Sympathetic  &  chol inergic  basal  forebrain  neurons   • First  neurotropic  factor  discovered   • Took  extracts  of  sympathetic  neurons,  applied  it  to  other  sympathetic  neurons,  you  can  grow  the   sympathetic  neuron  to  grow  in  a  dish  =  neural  growth  factor   • Extracted  ONE  protein  from  other  sympathetic  ganglia,  when  the  protein  is  appli ed  to  other  sympathetic   neurons,  this  neuron  suddenly  grows  lots  of  axons  and  dendrites   • One  protein  stimulated  nerve  growth   • When  this  nerve  growth  factor  was  applied  to  other  neurons,  there  was  no  effect   à  selective  for   sympathetic  neurons   • Very  specific  to  which  neurons  they  activate   • BDNF,  NT3,  NT4/5.   • Can  extract  growth  factors  from  brain   –  BNDF  (brain  derived  neurotropic  factors)   • Can  extract  growth  factors  from  glia  –  glial  factor   • Each  derived  from  cultured  cells  (sympathetic  neurons,  brain,  glia)  and  act   on  special  receptors  (Trk  and  p75)   • Act  by  way  of  neurotropic  receptors  (Trk  receptors,  p75  receptors)   • Neurotropic  factors  are  working  in  the  substrate,  can  be  released  by  different  cells   • BDNF  mainly  found  in  microglia   –  released  by  microglial  neurons,  stim ulates  receptors  on  sympathetic   neurons,  then  can  turn  on  growth  (stimulate  more  processes,  more  connections,  bigger  and  better   synaptic  connections)   • Chemical  induction  factor  that  allows  them  to  survive  or  not     Synaptic  Connections   • Neurons  matured  earlie r  can  make  axons  earlier  and  go  longer  distances   –  primary  cells  (big   output  cells)   • As  growth  cone  reaches  target,  they  start  making  synapses   • Once  attracted  by  some  tissue,  it  makes  hundreds  of  terminals  (one  axon  can  have   hundreds  of  terminals  on  lots  of   different  cells)   • Many  synapses  are  formed  initially.   • Proliferation  of  terminals  at  the  tip   • Most  of  these  synapses  are  eliminated  by  competition  between  inputs.   • Over  time,  diffuse  extra  connections  die  off   –  only  the  point-­‐for-­‐point  connections   survive  à  competitive  process   • Competition  involves  chemical  signals  (e.g.,  trophic  signals)  and  electrical  signals  (activity -­‐dependent  plasticity).   • More  inputsàmore  dendritesàmore  synapses.       Brain  Systems  for  Studying  Connections   • Crossing  fibres  of  ventral  spinal  co rd.  (netrin  attracts,  slit  repels  axons)       • Crossing  fibers  grow  by  crossing  midline  of  spinal   cord  by  being  attracted  by  netrin  at  first,  then   repelled  by  slit  as  it  leaves   • Retinotopic  maps  (2D)  in  the  tectum  of  the  superior   colliculus,  thalamus  and  cortex   • If  you  take  a  retina,  and  put  it  near  the  Colliculus,   those  retinal  axons  will  grow  out  towards  the   Colliculus  à  attracted  to  the  Colliculus   • How  is  the  2D  map  formed  on  the  Colliculus?   • As  they  go  into  the  Colliculus,  they  go  into  the   outer  layers,  then  segregate  so  that:   •  the  nose  end  and  back  end  of  the  retina   go  to  one  part  of  the  tectum   • and  the  dorsal  side  and  ventral  side  of  the   retina,  goes  to  the  other  part   • there  is  a  chemical  inside  the  Colliculus  (ephrin)   • there  is  a  2D  gradient  of  a  particular  prote in   • ephrin  A:  up  and  down;  ephrin  B:  side  to   side   • the  density  of  ephrin  is  located  so  that  there  is  low   ephrin  on  one  end,  and  high  ephrin  on  the  other   • nasal  neurons  go  to  high  ephrin  area ,  and   temporal  axons  go  to  the  low  ephrin  area   • the  growing  axons  read  the  density  of  ephrin  to   determine  where  they  terminate   • if  you  cut  out  half  of  the  retina,  they  still  maintain  this  gradient     • chemical  influences  how  they  approach,  and  how  they   avoid  to  form  connections   • efferent  levels  (up  &  down,  side  to  side)  determin es  which   retinol  fibers  connect  with  which  superior  Colliculus  area   • a  simple  chemical  gradient  that  determines  how  the   retinotopic  map  is  formed   • retinol  neurons  respond  to  this  gradient  to  form   connections,  which  makes  the  retinotopic  map   • Mutant  frog  with  3  eyes   rd • By  adding  a  3  eye  =  changes  in  connections   • Inputs  from  2  eyes  form  separate  columns  in  the   contralateral  tectum  –  retinotopic  maps   • When  there  is  3  eyes  innervating  the  tectum,  it  messes  up   the  maps  à  different  organization  within  the  left   Colliculus     o This  is  experimental  embryology:  change  the  embryo  by   changing  the  chemicals,  the  number  of  inputs,  where  those  inputs  enter  =  alter  way  the  brain  is  organized   • Mutant  flies  and  mice.   • In  experimental  embryology:  single  chemicals  can  change  the  growth,   single   genes  can  change  the  growth   à  influences  connections  and  behaviour   • Cerebellar  mutants,  weaver,  reeler.       Critical  Periods   • growth  in  Colliculus  occurs  early  in  development   à  before  animal  is  born   • specific  synaptic  connections  can  occur  prenatally  (ea rly  development  in   the  retina,  thalamus,  spinal)  or  later  in  time  (development  of  cortex  occurs   later)   • Synaptic  connections  formed  at   different  times  in  different  brain  areas.  These   times  are  critical  for  functional  development.   • Most  of  the  old  areas  in  th e  brain  occurs  prenatally   • Most  of  the  new  areas  (cortical  development)  occurs  postnatally   –  where   later  connections  of  the  cortex  occurs       • Lower  brain  earlier,  and  much  more  fixed  (occur  prenatally)  –  these  connections  are  determined  by  gene   expression  and  chemical  factors  =  more  fixed   • Same  in  all  animals   • Later  on,  these  are  influenced  by  neural  firings     • Neural  firings  occur  later  in  development  (especially  in  the  cortex  after  birth)   • Cortex  forms  after  birth,  connections  are  influenced  by  outside  environment.   • Cortical  connections  are  formed  by  a  new  cortical  chemical  =  NMDA  (glutamate  chemical)   • Cortical  connections  after  birth  are  influenced  by  firings  of  glutamate  neurons  (influenced  by  NMDA   receptors  after  neurons  fire  –  influenced  by  internal  activity  within  the  cortex)   • NMDA  is  important  for  memory,  cortical  development,  changing  throughout  lifetime  (synaptic  plasticity)   • Cortex  keeps  changing  throughout  life,  and  influences  thalamic  maps.   • Synaptic  plasticity  is  important  for  memory   –  synaptic  connections  are  constantly  changing       Electrical  Activity  and  Growth   • Retina:  Prenatal  waves  of  electrical  activity  in  each  eye  independently.   • Right  eye  active  first,  then  left   • Left  eye  has  a  brief  period  of  electrical  activity   • The  2  eyes  have  internal  factors  that  produ ce  electrical   exc
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